Role of the coagulation system in the local and systemic inflammatory response.
Activation of the coagulation cascade during the inflammatory response is an essential component of the host response to infection. Coagulation represents a double-edged sword. Necessary for hemostasis and the acute containment of an infective focus, it also amplifies the inflammatory response, decreases bacterial clearance, and in the critically ill patient contributes to end-organ damage and death. Evidence for these concepts is found in the fact that critically ill and septic patients consistently demonstrate marked abnormalities in their biochemical indices of coagulation. Moreover, there is excellent experimental evidence to suggest that replacement or inhibition of individual coagulation factors, either consumed or up-regulated during the inflammatory response, can attenuate both local and systemic injury and protect animals from otherwise fatal outcomes. Based on these facts, novel therapeutic approaches to the treatment of the systemic response to infection have been developed and tested in intensive care settings. Although promising results have been obtained, much work remains to be done in defining exactly which coagulation factors (or combination of factors) should be inhibited or replaced during treatment of the septic, critically ill patient. The experimental and clinical evidence linking the coagulation cascade to local and systemic inflammation is reviewed, and the status of the clinical trials performed to date is overviewed.
McGilvray
I D
ID
Department of Surgery, Toronto Hospital, Ontario, Canada.
Rotstein
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OD
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology*